Functional Roles of the Edited Isoform of GluA2 in GluA2-Containing AMPA Receptor Channels

G1uA2R is the edited isoform at the Q/R site of the AMPA receptor GluA2 subunit. In vivo, G1uA2R assembles with other AMPA receptor subunits into a high-conductance, tetrameric complex. Here we study the functional role of GluA2R in the context of G1uA1/2R and G1uA2Q/2R heteromeric receptors, using whole-cell recording and a laser pulse photolysis technique. We find the incorporation of G1uA2R with GluAl or G1uA2Q slows the channel-opening and channel-closing rates; for GluA2Q/2R, it further lowers EG(50), compared to the value of the GluA2Qhomomeric channels. When a conserved leucine-to-tyrosine (L -> Y) mutation is placed in each of these subunits, the L -> Y mutation exhibits a greater effect in GluA2R than in GluAl. Together, our results show GluA2R is the dominating isoform that shapes the overall functional properties of the G1uA2R-containing channels. Our results further suggest that glutamate most likely binds to G1uA2R with an EC50 of similar to 0.5 mM, rather than a non-G1uA2R subunit in a heteromeric AMPA receptor, and binding of two glutamate molecules to the two G1uA2R subunits is sufficient to initiate a conformational change, leading to the opening of the channel.